Gut microbiota in HIV-pneumonia patients is related to peripheral CD4 counts, lung microbiota, and in vitro macrophage dysfunction.

Pneumonia is common and frequently fatal in HIV-infected patients, due to rampant, systemic inflammation and failure to control microbial infection. While airway microbiota composition is related to local inflammatory response, gut microbiota has been shown to correlate with the degree of peripheral immune activation (IL6 and IP10 expression) in HIV-infected patients. We thus hypothesized that both airway and gut microbiota are perturbed in HIV-infected pneumonia patients, that the gut microbiota is related to peripheral CD4+ cell counts, and that its associated products differentially program immune cell populations necessary for controlling microbial infection in CD4-high and CD4-low patients. To assess these relationships, paired bronchoalveolar lavage and stool microbiota (bacterial and fungal) from a large cohort of Ugandan, HIV-infected patients with pneumonia were examined, and in vitro tests of the effect of gut microbiome products on macrophage effector phenotypes performed. While lower airway microbiota stratified into three compositionally distinct microbiota as previously described, these were not related to peripheral CD4 cell count. In contrast, variation in gut microbiota composition significantly related to CD4 cell count, lung microbiota composition, and patient mortality. Compared with patients with high CD4+ cell counts, those with low counts possessed more compositionally similar airway and gut microbiota, evidence of microbial translocation, and their associated gut microbiome products reduced macrophage activation and IL-10 expression and increased IL-1β expression in vitro. These findings suggest that the gut microbiome is related to CD4 status and plays a key role in modulating macrophage function, critical to microbial control in HIV-infected patients with pneumonia

CP^{N-1} models and the Quantized 2D Black Holes

We have examined the coupled system of the dilaton gravity and the $CP^{N-1}$ theory known as a model of the confinement of massive scalar quarks. After the quantization of the system, we could see the quantum effect of the gravitation on the coupling constant of $CP^{N-1}$ model and how the coupling constant of dynamically induced gauge field changes near the black hole configuration.Comment: 12 pages, Late

Bayesian Inference in Processing Experimental Data: Principles and Basic Applications

This report introduces general ideas and some basic methods of the Bayesian probability theory applied to physics measurements. Our aim is to make the reader familiar, through examples rather than rigorous formalism, with concepts such as: model comparison (including the automatic Ockham's Razor filter provided by the Bayesian approach); parametric inference; quantification of the uncertainty about the value of physical quantities, also taking into account systematic effects; role of marginalization; posterior characterization; predictive distributions; hierarchical modelling and hyperparameters; Gaussian approximation of the posterior and recovery of conventional methods, especially maximum likelihood and chi-square fits under well defined conditions; conjugate priors, transformation invariance and maximum entropy motivated priors; Monte Carlo estimates of expectation, including a short introduction to Markov Chain Monte Carlo methods.Comment: 40 pages, 2 figures, invited paper for Reports on Progress in Physic

Matrix and Tensor Factorization Methods for Toxicogenomic Modeling and Prediction

Peer reviewe

Examining the quality and management of non-geometric building information modelling data at project hand-over

Through the exponential global increase of Building Information Modelling (BIM) adoption across the Construction industry, and the emergence of inter-connected, strategic and data-rich solutions; such as Big Data, the Internet of Things and Smart Cities, the importance associated with activities and decisions reliant on exact data input, transaction, analysis, and resulting actions becomes exponentially magnified. The supply of inaccurate BIM data may negatively impact on systems and processes that require fully assured data of appropriate quality/veracity, to support informed decision making, deliver functionality, facilitate services, or direct strategic actions within the built environment. This preliminary research intends to provide a catalyst for discussion, analysis and information retrieval relating to Building Information Modelling (BIM) processes where non-geometric data errors may; or are predicted to occur within a project environment. This may result in the delivery of data that cannot be described as representing truth or of good quality, and therefore of little value or use to the data user. The wider aspects of this research investigates specifically non-geometric data veracity & associated dimensions of data quality; in order to discover and explore future solutions to resolve current industry data quality assessment challenges. This paper provides feedback from the research focusing on the current state, presenting existing industry challenges and proposes further research areas based on initial findings

The Social Relations Approach, empowerment and women factory workers in Malaysia

This article discusses the empowerment of women factory workers in Malaysia through the lens of Kabeer’s Social Relations Approach. The approach offers an institutional analysis of how gender inequality is produced and calls for the overall terms of exchange and cooperation to be shifted in women’s favour. Its application shows that Malaysian women factory workers face significant challenges, due to the character of institutions, and women’s difficulties in adopting and internalising the notion of ‘empowerment’

Distinct lung microbiota associate with HIV-associated chronic lung disease in children.

Chronic lung disease (CLD) is a common co-morbidity for HIV-positive children and adolescents on antiretroviral therapy (ART) in sub-Saharan Africa. In this population, distinct airway microbiota may differentially confer risk of CLD. In a cross-sectional study of 202 HIV-infected children aged 6-16 years in Harare, Zimbabwe, we determined the association of sputum microbiota composition (using 16S ribosomal RNA V4 gene region sequencing) with CLD defined using clinical, spirometric, or radiographic criteria. Forty-two percent of children were determined to have CLD according to our definition. Dirichlet multinomial mixtures identified four compositionally distinct sputum microbiota structures. Patients whose sputum microbiota was dominated by Haemophilus, Moraxella or Neisseria (HMN) were at 1.5 times higher risk of CLD than those with Streptococcus or Prevotella (SP)-dominated microbiota (RR = 1.48, p = 0.035). Cell-free products of HMN sputum microbiota induced features of epithelial disruption and inflammatory gene expression in vitro, indicating enhanced pathogenic potential of these CLD-associated microbiota. Thus, HIV-positive children harbor distinct sputum microbiota, with those dominated by Haemophilus, Moraxella or Neisseria associated with enhanced pathogenesis in vitro and clinical CLD

Comparative analysis of inflamed and non-inflamed colon biopsies reveals strong proteomic inflammation profile in patients with ulcerative colitis

<p>Abstract</p> <p>Background</p> <p>Accurate diagnostic and monitoring tools for ulcerative colitis (UC) are missing. Our aim was to describe the proteomic profile of UC and search for markers associated with disease exacerbation. Therefore, we aimed to characterize specific proteins associated with inflamed colon mucosa from patients with acute UC using mass spectrometry-based proteomic analysis.</p> <p>Methods</p> <p>Biopsies were sampled from rectum, sigmoid colon and left colonic flexure from twenty patients with active proctosigmoiditis and from four healthy controls for proteomics and histology. Proteomic profiles of whole colonic biopsies were characterized using 2D-gel electrophoresis, and peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for identification of differently expressed protein spots.</p> <p>Results</p> <p>A total of 597 spots were annotated by image analysis and 222 of these had a statistically different protein level between inflamed and non-inflamed tissue in the patient group. Principal component analysis clearly grouped non-inflamed samples separately from the inflamed samples indicating that the proteomic signature of colon mucosa with acute UC is strong. Totally, 43 individual protein spots were identified, including proteins involved in energy metabolism (triosephosphate isomerase, glycerol-3-phosphate-dehydrogenase, alpha enolase and L-lactate dehydrogenase B-chain) and in oxidative stress (superoxide dismutase, thioredoxins and selenium binding protein).</p> <p>Conclusions</p> <p>A distinct proteomic profile of inflamed tissue in UC patients was found. Specific proteins involved in energy metabolism and oxidative stress were identified as potential candidate markers for UC.</p